Some factors affecting cerebral tissue saturation during obstructive sleep apnoea.

Measurement of cerebral tissue saturation during obstructive sleep apnoea (OSA) may provide additional information to conventional peripheral oxygen saturation. Thirteen subjects with OSA (mean apnoea/hypopnoea index 65.7+/-27.9) were monitored using full polysomnography and monitoring of near-infrared cerebral tissue oxygenation index (TOI). One-thousand and thirty-six apnoeas and hypopnoeas were analysed, in terms of duration, sleep stage, arterial oxygen saturation (Sa,O2) dip, minimum Sa,O2, TOI dip and minimum TOI. Cerebral TOI is a measure of cerebral tissue saturation of haemoglobin with oxygen, calculated using near-infrared spatially resolved spectroscopy, which has been shown to have a high specificity for intracranial changes. Decreases in cerebral oxygenation were observed during apnoeas and hypopnoeas. Baseline TOI ranged from 50.1-73.0% and mean apnoea/hypopnoea related TOI dips ranged from 1.43-6.85%. Mean Sa,O2 dips varied from 3.8-21.7%. In regression analysis, factors significantly predicting the magnitude of the TOI dip were Sa,O2 dip, minimum Sa,O2, apnoea duration and rapid eye movement sleep stage. The effect of apnoea duration and sleep stage remained significant after Sa,O2 was included in the regression equation. Near-infrared spectroscopy provides a noninvasive technique for monitoring cerebral tissue saturation during obstructive sleep apnoea.

Long-term use of mandibular advancement splints for snoring and obstructive sleep apnoea: a questionnaire survey.

A mandibular advancement splint (MAS) may be an alternative treatment for snoring and obstructive sleep apnoea (OSA). However, there is little subjective or objective information concerning long-term effectiveness, compliance and side effects. A retrospective questionnaire was used to survey these issues plus patient satisfaction and maintenance requirements in 166 patients who could have worn a mandibular advancement splint for over a year. One-hundred and twenty-six (76%) subjects returned the questionnaire, (84 with OSA, 42 snorers), of whom 69 (55%) reported still using the splint regularly, 47 (37%) every night. The most common reported reasons for stopping use were discomfort (29/ 57; 52%) of nonusers), and poor perceived efficacy (12 subjects). Users reported more daytime symptoms, and they and their partners were more likely to observe improvements with splint use. Side effects were reported by 49 subjects, more commonly in nonusers. Sixty-five of 67 current users and 23 of 41 nonusers reported less snoring with splint use (p = < 0.001). Long-term mandibular advancement splint usage appeared less satisfactory than previously reported, however, splints were considered effective by 97% of current users and even by over half of those who had stopped use. Reasons for stopping use included side effects, social circumstances, dental treatment, as well as lack of perceived efficacy.

Systemic bioavailability and potency of high-dose inhaled corticosteroids: a comparison of four inhaler devices and three drugs in healthy adult volunteers.

OBJECTIVES: To compare the systemic bioavailability (assessed by cortisol suppression) of high-dose budesonide when given by four inhaler devices and orally. Also studied are the relative systemic potencies of three inhaled steroids (budesonide, fluticasone propionate, and beclomethasone dipropionate) when given by metered-dose inhaler (MDI) with a large volume spacer. DESIGN: Double-blind, crossover, placebo-controlled trial. PARTICIPANTS: Sixteen healthy, steroid-naive adult volunteers. METHODS: On separate occasions, each subjects took 4 mg of budesonide through the following devices: MDI alone, MDI with 750-mL. spacer, dry-powder inhaler and nebulizer; 4 mg of budesonide was also taken orally to assess the effects of GI absorption. For the drug comparison, each subject took 4 mg of budesonide, fluticasone, and beclomethasone, and 2 mg of budesonide and fluticasone by MDI and spacer. RESULTS: Greatest percent suppression (95% confidence interval) of 9:00 AM cortisol with budesonide was observed with MDI alone (73% [57 to 90]) and turbohaler (72% [58 to 86]) compared with MDI spacer (42% [22 to 64]) and oral administration (14% [+6- to -34]). Nebulized budesonide produced an insignificant rise in 9:00 AM cortisol level. The most suppressive drug (given by MDI spacer) was fluticasone at 4 mg (86% [82 to 91]) and at 2 mg (72% [59 to 85]). The least suppressive drug was budesonide at 4 mg (43% [22 to 64]) and at 2 mg (25% [3 to 47]). The effects of 4 mg of beclomethasone were intermediate (66% [49 to 82%]). CONCLUSIONS: The choice of delivery device for administration of budesonide can lead to important differences in systemic bioavailability. Fluticasone has greater systemic potency than budesonide or beclomethasone when given at microgram equivalent dosage. The systemic potency ratio of fluticasone propionate to budesonide in normal human volunteers in the present study is similar to the therapeutic potency ratio of the drug in asthmatic patients (approximately 2:1).

Airway endothelin levels in asthma: influence of endobronchial hypertonic saline challenge.

BACKGROUND: The pathophysiology of exercise-induced asthma is not well understood. Hypertonicity of the airway lining fluid resulting from loss of water due to hyperventilation is considered to play a role, but the precise mechanism by which hypertonicity can induce bronchoconstriction is unknown. Peptides of the endothelin (ET) family have potent smooth muscle contractile properties, and have been linked to airway narrowing in stable asthma. We postulated that ET release may contribute to the acute bronchoconstrictor response induced by a hypertonic stimulus. METHODS: Seven male asthmatic subjects underwent local endobronchial challenge with hypertonic (3.6%) saline and, as a control, isotonic (0.9%) saline aerosols in separate bronchopulmonary segments. Bronchoalveolar lavage (BAL) was performed at both sites during the phase of immediate bronchoconstriction. Concentrations of immunoreactive ET and of the mast cell products, histamine, tryptase and prostaglandin D2, in BAL fluid were measured. RESULTS: Concentrations of ET in BAL fluid from the hypertonic saline-challenged sites were significantly lower than those in BAL fluid from sites exposed to isotonic saline (0.19 [0.11-1.24] fmol/mL vs. 0.40 [0.20-2.36] fmol/mL, P<0.05). Concentrations of histamine, tryptase, and prostaglandin D2 did not differ significantly between the two sites. CONCLUSIONS: These findings do not support the hypothesis that ET release within the airway lumen is involved in the bronchoconstrictor response induced by hypertonic saline.

Accelerated ultraviolet aging of intraocular lens optic materials: a 50 year simulation.

PURPOSE: To introduce an updated accelerated photoaging model for application to intraocular lens (IOL) materials and to apply this model to determine the photostability of AMO PhacoFlex model SI-18NGB and PhacoFlex II model SI-20NGB silicone IOL materials over a simulated 50 years of exposure. SETTING: Research laboratory, AMO Surgical Products, Irvine, California, USA. METHODS: Previous photoaging models and aging parameters, including intraocular exposure intensity, daily exposure duration, and acceleration exponent were critically reviewed and analyzed, and an updated model was introduced. The test specimens were continuously irradiated with ultraviolet (UV) light in a Suntest UV chamber at an intensity of 8 mw/cm2 for 86 days to simulate 50 years of in vivo exposure. The silicone lenses were evaluated for focal length, resolution, and surface integrity, while regular slabs were tested for tensile strength, elongation, hardness, contact angle, and percentage light transmission. The UV-absorption capacity was monitored using ultrathin slabs (0.127 mm). Six replicate samples were used for each determination, and a two-sided t-test with significance set at P < .05 was used to evaluate the difference before and after aging. RESULTS: No significant difference in optical, physical, and surface properties of the lenses and lens materials was found. No change in UV-absorption capacity was observed after a simulated 50 years of accelerated photoaging. CONCLUSION: The AMO PhacoFlex SI-18NGB and PhacoFlex II SI-30NGB silicone lens materials resisted UV light degradation over 50 years of simulated exposure.

Cross refractoriness between bradykinin and hypertonic saline challenges in asthma.

BACKGROUND: Repeated inhalation of bradykinin and hypertonic saline leads to refractoriness of the bronchoconstrictor response in asthma. It is not known whether cross-refractoriness exists between these stimuli. OBJECTIVE: We postulated that repeated bradykinin and hypertonic saline bronchial challenges might reduce the airway response to subsequent hypertonic saline and bradykinin challenges, respectively. METHODS: Eleven atopic asthmatic subjects underwent two concentration-response studies, separated by 1 hour, with either inhaled histamine or bradykinin. After recovery, a hypertonic saline challenge was performed. During the next phase, nine subjects underwent two concentration-response studies, separated by 1 hour, with hypertonic saline. After recovery, a bradykinin challenge was performed. RESULTS: On the histamine study day, the mean provocative volume of agonist required to produce 20% drop in forced expiratory volume in 1 second (PD20) hypertonic saline was 220.7 L (+/- 42.7 L) and this was not significantly different from that measured at baseline. On the bradykinin study day, the geometric mean provocative concentration of agonist required to produce a 20% drop in forced expiratory volume in 1 second (PC20) was 0.39 mg/ml (0.01 to 11.73 mg/ml) for the first test and significantly higher at 1.38 mg/ml (0.01 to > 16.0 mg/ml) for the second test (p = 0.006). The hypertonic saline PD20 increased significantly from a baseline of 159.2 L (+/- 27.3 L) to 377.6 (+/- 64.7 ) (p = 0.003). On the hypertonic saline study day, the mean PD20 was 152.8 L for the first test, and 337.7 L for the second test (p = 0.01). PC20 bradykinin increased significantly from a baseline of 0.57 to 2.56 mg/ml (p = 0.02). A significant correlation was found between loss of response to bradykinin and to hypertonic saline (rs, 0.63 and 0.76). CONCLUSION: Refractoriness produced by repeated exposure of the airways to bradykinin and hypertonic saline results in loss of responsiveness to hypertonic saline and bradykinin respectively, suggesting a shared mechanism for refractoriness produced by these stimuli.

Dysphagia due to secondary achalasia as an early manifestation of squamous cell carcinoma.

A 59-year-old man, a smoker, presented with features of airflow obstruction due to squamous cell carcinoma of central airways mimicking chronic obstructive airways disease. He also had pronounced dysphagia. Computed tomographic and magnetic resonance imaging scans showed mediastinal tumour invasion but no direct oesophageal involvement. Oesophageal manometry studies revealed that dysphagia was due to the oesophageal motility disorder, secondary achalasia.

Effect of silicone sound speed and intraocular lens thickness on pseudophakic axial length corrections.

We compared the sound speeds of SLM-1/UV (990 M/sec at 35 degrees Celsius [degrees C]), SLM-2/UV (1090 M/sec at 35 degrees C), and Perspex CQ poly(methyl methacrylate)(2658 M/sec at 35 degrees C). Methods are presented to determine the correction of axial length (CAL) factors for axial length measurements made on pseudophakes with AMO PhacoFlex Si-18, Si-26 (SLM-1/UV), and AMO PhacoFlex II SI-20 or SI-30 (SLM-2/UV) silicone intraocular lenses (IOLs). A CAL is required to avoid potential errors with secondary IOL power predictions; CALs, which are strongly dependent on the material sound speed and less so on lens thickness, ranged from -0.65 mm to -1.20 mm for SLM-1/UV silicone IOLs and from -0.35 mm to -0.55 mm for SLM-2/UV silicone IOLs. The sound speeds of IOL materials varied insignificantly between ambient room temperature (23 degrees C) and intraocular temperature (35 degrees C).

Airway effects of local challenge with hypertonic saline in exercise-induced asthma.

Hypertonicity of airway lining fluid has been suggested as the stimulus for bronchoconstriction in exercise-induced asthma. We explored the airway effects of delivering a direct hypertonic stimulus to asthmatic airways via a fiberoptic bronchoscope, comparing hypertonic saline challenge by direct instillation with local aerosol delivery. A group of 18 asthmatic subjects responsive to inhaled hypertonic saline with a history of EIA were studied; the first 9 subjects received local challenge with hypertonic saline by direct instillation, and the next 9 subjects were challenged by local aerosol delivery. A control challenge with isotonic saline by either instillation or aerosol was performed at a same bronchoscopy. Local challenge with hypertonic saline by aerosol delivery was found to be more effective in inducing local bronchoconstriction (8 of 9 subjects) than instillation (2 of 6 subjects). Paired BAL fluid samples and bronchial biopsies were obtained in total of 11 and 9 subjects, respectively. Local challenge with hypertonic saline either by instillation or aerosol produced no significant change in histamine, tryptase, or PGD2 levels in BAL fluid or mast cell numbers and degranulation in bronchial biopsies. A significant correlation was observed between histamine levels in BAL fluid and airway responsiveness to inhaled hypertonic saline (rs = -0.59, p < 0.05). Bronchial biopsies showed evidence of extensive epithelial damage; however, this was not related to airway responsiveness to inhaled hypertonic saline.

Investigative use of fibreoptic bronchoscopy for local airway challenge in asthma.

Local airway challenge has advantages over inhalation bronchial challenge as the response of the airway can be restricted and directly observed. It has been safely performed in subjects with mild or moderate asthma, either by the direct instillation of challenge solution to the selected segmental airways via a bronchoscope, or delivered to an airway segment isolated with a double-balloon catheter. However, these techniques carry potential complications, such as generalized wheeze, and due care is required in selection of subjects. Most investigators have used the method for studying the airway events following allergen challenge. Others have studied the airway changes following challenge with non-allergen provocation agents, such as hypertonic saline, adenosine 5'-monophosphate and cold dry air. The method has helped to define changes in the inflammatory cells and mediators in relation to early and late airway responses to allergen. Similarly, study of airway events following local challenge with hypertonic solution has provided useful knowledge in understanding the mechanisms of exercise-induced asthma. With more experience and an improved margin of safety, it will be possible to study local changes in airway physiology following local airway challenge. Finally, the techniques also have potential use for studying the airway events following provocation with a wide range of agents of potential relevance to the pathogenesis of asthma.

The contribution of neurogenic reflexes to hypertonic saline-induced bronchoconstriction in asthma.

BACKGROUND: Hypertonic saline induces bronchoconstriction in most patients with asthma; however, the mechanisms involved are not clearly understood. We have investigated the role of neurogenic mechanisms in hypertonic saline-induced bronchoconstriction. METHODS: The effect of pretreatment with the anticholinergic drugs atropine and ipratropium bromide and the local anesthetic drug lidocaine on hypertonic saline responsiveness was studied in 11 subjects with asthma. Ultrasonically nebulized hypertonic saline challenge was given in a dose-response manner to determine the provocative dose of hypertonic saline-laden air required to produce a fall in forced expiratory volume in 1 second (FEV1) of 20% or greater (PD20HS). A control PD20HS with no pretreatment was measured before randomization, and on the next three visits PD20HS was determined after pretreatment with each of the following: intramuscularly administered atropine, inhaled ipratropium bromide, and inhaled lidocaine. RESULTS: The baseline mean FEV1 values increased by 3.5% and 4% 30 minutes after administration of atropine and ipratropium bromide, respectively, and decreased by 5.8% at 10 minutes after inhalation of lidocaine. These changes in the baseline FEV1 were not significant and did not have any effect on the PD20HS response. Premedication with atropine, ipratropium bromide, and lidocaine resulted in increases of 2.5, 2.0, and 2.6 times in mean PD20HS, respectively. CONCLUSIONS: The protection afforded by the drugs was variable in the individual subjects and not related to age, sex, baseline FEV1, provocative concentration of histamine causing a 20% fall in FEV1 or use of the inhaled corticosteroids. The protection afforded by anticholinergic and local anesthetic drugs suggests the contribution of neurogenic reflexes in the pathogenesis of hypertonic saline-induced bronchoconstriction in asthma.

The protective effect of inhaled leukotriene D4 receptor antagonist ICI 204,219 against exercise-induced asthma.

Leukotrienes are potent bronchoconstrictors, and they are present in the airways of asthmatic subjects. Leukotriene receptor antagonists given intravenously or orally prior to exercise attenuate the bronchoconstrictor response to exercise in asthma. We have determined the prophylactic effect of an inhaled leukotriene D4-receptor antagonist ICI 204,219 (400 micrograms) against exercise-induced bronchoconstriction in nine asthmatic subjects in a randomized, placebo-controlled, double-blind, cross-over study. Exercise challenge was performed on a cycle ergometer at a predetermined work load that was kept constant throughout the study. A "screening" and a "run-in" exercise test were performed to determine the reproducibility of the challenge. ICI 204,219 or matched placebo was given 30 min prior to exercise challenge, and bronchoconstriction after exercise was assessed as change in FEV1 over 30 min. There was no significant effect on baseline airway caliber at 20 min after inhalation of ICI 204,219. ICI 204,219 significantly inhibited the bronchoconstrictor response to exercise. The mean maximal percentage fall in FEV1 after exercise was 14.5% as compared with the placebo of 30.2% (p = 0.043), and the area under curve (AUC) for FEV1 during the first 30 min (AUC0-30) after exercise was significantly reduced (p = 0.043). The time for recovery of FEV1 to 5% of baseline was also significantly shorter with ICI 204,219 than with placebo (median, 20 versus 60 min; p = 0.018). The protection against exercise-induced bronchoconstriction provided by ICI 204,219 was variable, with almost complete inhibition of the response in three subjects, partial inhibition in another three subjects, and no protection in three subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of the hypertonic saline responsiveness of the airways to exercise induced asthma symptom severity and to histamine or methacholine reactivity.

BACKGROUND: Conflicting views exist over whether responsiveness of the airways to hypertonic saline relates to non-specific bronchial hyperresponsiveness measured by histamine or methacholine challenge. The bronchoconstrictor responses to exercise and hypertonic saline are reported to be closely related, but the relationship between the symptoms of exercise induced asthma and airway responsiveness to hypertonic saline is not known. METHODS: In 29 asthmatic patients with a history of exercise induced asthma, the response to an ultrasonically nebulised hypertonic saline (3.6% sodium chloride) aerosol, measured as the volume of hypertonic saline laden air required to produce a fall in forced expiratory volume in one second (FEV1) of > or = 20% (PD20), was compared with the concentration of histamine (PC20; group 1) and methacholine (PC20; group 2) producing a 20% fall in baseline FEV1 and exercise induced asthma symptom severity score (groups 1 and 2). The hypertonic responsiveness was determined in a dose-response manner to a maximum dose of 310 1 and the exercise induced asthma symptom severity was scored on a scale of 0-5. RESULTS: Of the 29 patients, 23 (79%) were responsive to the hypertonic saline, with PD20 values ranging from 9 to 310 1. A significant correlation was found between the PD20 hypertonic saline and the exercise induced asthma symptom score. There was no significant correlation between the PD20 response to hypertonic saline and the histamine PC20 or methacholine PC20. The exclusion of those subjects who failed to respond to hypertonic saline improved the relationship between hypertonic saline and methacholine PC20. No significant correlation was found between the exercise induced asthma symptom score and histamine PC20 or methacholine PC20. CONCLUSION: These findings suggest that hypertonic saline responsiveness bears a closer relationship to the severity of exercise induced asthma symptoms than to the non-specific bronchial hyperresponsiveness measured by histamine or methacholine reactivity.